It is well established that the activity of the immune system declines with advancing age in several species, including the rat, and that thyroid hormone is required for the maintenance of normal immune function. In addition, several studies have indicated that tissue responsiveness to thyroid hormone decreases with advancing age. This raises the possibility that the age-related decline in the immune competence is a consequence, at least in part, of a decrease in the response of the lymphoid tissue to the thyroid hormone. We propose to explore this hypothesis in the rat, using as response indices a) several metabolic functions that are necessary for or related to mitogen-induced lymphocyte transformation, and that we have shown to be stimulated by thyroid hormone, and b) several immunological functions, in particular mitotic activity induced by mitogenic agents, that have been suggested to be affected, directly or indirectly, by thyroid status. We will first examine the in vitro activities of the metabolic functions and their stimulation by triiodothyronine in lymphoid cells from animals of varying age. We also propose to examine the effects of changes in the in vivo thyroid status on the in vitro metabolic and mitotic functions of lymphoid tissue and its responsiveness to T3 and to the mitogens.